HIV gp41 is a heavily glycosylated transmembrane protein. The difficulty in producing full length recombinant gp41 requires an incremental approach for structural determination studies. The ectodomain region, located on the outer surface of the viral membrane directly mediates membrane fusion events via an N-terminal fusion domain (FD). In our previous work both the NMR and X-ray structures of a truncated gp41 ectodomain (lacking FD) were determined. Both methods indicated a rod-like trimer comprising three parallel N-terminal alpha-helices assembled as a coiled-coil in the center with three antiparallel C-terminal alpha-helices packed on the outside with highly flexible loops connecting the inner and outer helices (6-helical bundle: 6HB). Recently, we described the structure of the FD which consists of an N-terminal helix with a C-terminal linker region. To understand in more detail the interaction between the fusion domain, and the rest of the ectodomain, constructs were made which included the whole of the ectodomain and the region anchoring it into the viral membrane: N-terminal FD- 6 HB - linker region - transmembrane region. This complex membrane protein which contains two membrane associating regions (FD and transmembrane domain) was expressed in bacteria and purified as a protein-detergent complex. Using analytical ultracentrifugation and other biophysical methods, the protein complex was shown to be physical homogenous and readily formed crystals. Currently, the diffraction resolution of the crystals is not high enough for detailed structure determination -this is a common occurrence with protein-detergent systems. Attempts to improve the quality of the crystals continue and in parallel the structure of the membrane protein system is being studied using high resolution NMR spectroscopy. It is hoped that these structural studies will provide insight into the fusion mechanism and so provide direction for alternative anti-HIV therapeutic approaches.